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SHR Neuro Cancer Cardio Lipid Metab Microb
Louch, WE; Bito, V; Heinzel, FR; Macianskiene, R; Vanhaecke, J; Flameng, W; Mubagwa, K; Sipido, KR.
Reduced synchrony of Ca2+ release with loss of T-tubules-a comparison to Ca2+ release in human failing cardiomyocytes.
Cardiovasc Res. 2004; 62(1):63-73
Doi: 10.1016/j.cardiores.2003.12.031
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- Co-authors Med Uni Graz
- Heinzel Frank
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- Abstract:
- OBJECTIVES: During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release. METHODS: Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging. RESULTS: Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density. CONCLUSIONS: Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium - metabolism
- Cells, Cultured - metabolism
- Electrophysiology - metabolism
- Heart Failure, Congestive - metabolism
- Humans - metabolism
- Image Processing, Computer-Assisted - metabolism
- Microscopy, Confocal - metabolism
- Myocytes, Cardiac - metabolism
- Sarcoplasmic Reticulum - ultrastructure
- Swine - ultrastructure
- Find related publications in this database (Keywords)
- heart failure
- calcium
- cell culture
- E-C coupling
- myocytes
- SR (function)
- sarcolemma
- T-tubules
- pig
- confocal microscopy